Hepatitis A virus (HAV) is a member of the Picornaviridae (Melnick, J. L. (1982), Intervirology, 18, 105-106). It is endemic throughout the world and can cause large outbreaks of disease (W.H.O. 1988, Weekly Epidemiological Record, 65, 91-92). Protection is afforded by administration of immune human IgG as at present there is no vaccine available. Killed virus vaccines are now under clinical trials but the production of a cost-effective vaccine is hampered by the low yields of virus obtained from tissue culture systems. Attempts have been made to improve the virus yield and it has been reported that the cellular RNA polymerase-2 inhibitor 5,6-dichloro1-.beta.-d-ribofuranosylbenzimidazole increases yields by 200-300% when incorporated into the culture medium.
A demonstration that HAY would grow in tissue culture (Provost, P. J. & Hillerman, M. R. (1979), Proceeding Society Experimental Biology and Medicine, 160, 213-221) was a considerable advance for the study of the virus. Since that time strains of hepatitis A have been developed that grow more rapidly and to a higher titre than the original isolates. However, compared to other picornaviruses, the yields are still low and the time to obtain maximum yield is long. There are reports that the use of host enzyme inhibitors can increase the yield of HAV (Widdell, A., Hansson, B. G., Nordenfelt, E. and Oberg, B. (1988), Journal of Medical Virology, 24, 369-376), however these are expensive and are unlikely to be cost effective for virus production for the preparation of vaccines.